3054 — Psychotropic Pharmacotherapy Associated with QT Prolongation among Veterans with Posttraumatic Stress Disorder

Zeber JE, Central Texas VA; Stock EM, Central Texas VA; McNeal CJ, Baylor Scott & White; Banchs JE, Baylor Scott & White; Copeland LA, Central Texas VA;

Objectives:
In cardiology, the QT interval is the time between two waves in the heart's electrical cycle; a prolonged QT interval increases risk for ventricular tachyarrhythmias and sudden death. The VA prevalence of QT prolongation is 17 per 100,000 patients, this rate doubling among individuals with any serious mental illness. In addition to several patient factors, 3% of all prescriptions are for drugs associated with potential QT prolongation including antibiotics, antiepileptics, and antipsychotic agents. In 2012, the FDA issued a "black box" warning adding citalopram to this list, a selective serotonin reuptake inhibitor (SSRI) commonly used for posttraumatic stress disorder (PTSD).

Methods:
We identified all Veterans with PTSD in 2006-2009, with 176 patients also diagnosed with QT prolongation. These cases were matched 1:4 on age, gender, visit date and setting, and physical comorbidity. Classification trees (CART) assessed QT prolongation risk among prescribed medications for the combined sample (N = 880). Additionally, proportional hazards regression models estimated the association between QT prolongation and mortality, adjusting for demographics and comorbidities.

Results:
Receipt of any drug with known QT prolongation risks varied by group (23 percent cases vs. 15 percent controls, p < 0.01). Psychotropic medications conferring particular risks included the antipsychotic ziprasidone and the anxiolytic buspirone, each tripling the QT prevalence, but not the SSRIs citalopram and fluoxetine. Classification trees found sotalol and the antidepressant amitriptyline carried greater risk among cardiac patients, and methadone, especially if prescribed with quetiapine, among non-cardiac patients. Overall, QT prolongation significantly increased the risk for mortality (HR = 1.60; CI: 1.04-2.44).

Implications:
Certain common medications are associated with cardiac concerns in patients with PTSD with a range of physical or mental health comorbidities, thus individuals frequently taking multiple drugs, leading to greater mortality risks. Powerful analytical decision models such as CART are particularly advantageous when exploring nonlinear relationships or interactions in patients with complex treatment needs.

Impacts:
These findings may potentially impact clinical decision-making for an increasing population of Veterans with PTSD and related conditions. For patients at higher risk of QT prolongation, antidepressants other than amitriptyline should be considered. Furthermore, medications for comorbid conditions, notably substance abuse, should be closely monitored for heightened QT prolongation risk.